Immune response genes in mice provide an opportunity to study mechanisms governing immunity. We identified several T-cell membrane glycoproteins controlled by the immune response region (I-region) of the mouse H-2 gene cluster on chromosome 17. Early experiments suggested that the I region contained structural genes for these glycoproteins. Recent evidence indicates that I-region genes control expression of structural genes located elsewhere in the genome. I region-controlled T-cell glycoproteins may participate in immunoregulatory interactions among lymphocytes and macrophages. Specifically, these glycoproteins may be T-cell receptor structures adapted to distinguish "self." Our goal is to characterize these glycoproteins genetically and biochemically and to determine the relationship between their expression and T-cell function. T-cell I-J-encoded structures are shielded by protease-susceptible material. Extended proteolysis removed them. T-cell surface I-J expression results from the action of at least two complementing genes. One gene is within the H-2 region; the second gene, termed Jt, is on chromosome 4. Recombinant mouse strains B10.A(3R) and B10.A(5R) and strains B10.HTT and B10.S(9R) do not differ at the H-2k locus required for I-Jk expression. This locus maps to the right of B10.A(4R) recombination. The I-Jk determinant recognized by monoclonal antibodies involves alpha-D-mannosyl residues associated with protein. We investigated genes in the chromosomal segment between K and I-A. Using three different strain combinations, we produced antibodies specific for a T-lymphocyte determinant, Iat.W41, controlled by genes in the Kk to I-Ak interval. In addition to a strong mixed leukocyte reaction, genes between K and I-A contribute to a graft-versus-host reaction. (LB)